One-pot SSA-catalyzed b-elimination an efficient and

Neuc2en1Me per-OAc, the fully protected glycal of sialic acid, is a key intermediate in the discovery of therapeutics and diagnostics, including anti-influenza drugs and proteolysis resistant peptidomimetic foldamers. The synthesis of this sialic acid derivative, however, still relies on standard sugar chemistry that utilizes multi-step methodologies. Herein we report a facile and highly efficient microwave-assisted preparation of Neuc1Me using silica sulfuric acid (SSA) as solid-supported acid catalyst that is one- to two-orders of magnitude faster than standard procedures. We also describe the microwave-assisted and SSA-catalyzed one-pot, rapid, solvent free reaction that combines both peracetylation and b-elimination reactions in one step to generate the glycal from Neuc1Me. We coined the term One-pot SSA-catalyzed Technology for b-Elimination Protocol (OneSTEP) to describe this least laborious, most efficient, and practical preparation to date of Neuc2en1Me per-OAc in terms of yield, time, reagent cost, and waste generation.